Dr. Julie Park seeks to become an innovative and independent clinical investigator committed to understanding different aspects of neuroblastoma therapy. Using two distinct but complementary strategies, she will address two critical clinical challenges in the treatment of high risk neuroblastoma the failure to achieve an initial complete or partial response to induction therapy and the failure of consolidation therapy to control minimal residual disease MRD) at metastatic sites, particularly the marrow and adjacent cortical bone. Topotecan has shown promising anti-leuroblasotma activity and has synergistic activity with standard agents used in the treatment of neuroblastoma. Dr. Park will conduct a pilot study to test the feasibility of adding topotecan to standard active agents in nueroblastoma in an intensively dosed chemotherapy induction regimen with the goal of improving initial tumor response rates. The pilot study will be developed within the national cooperative Children's Oncology Group (COG) and as such will also provide training in the development and implementation of cooperative group trials. Despite the importance of achieving maximal initial tumor response, elimination of chemotherapy-refractory MRD, particularly within metastatic sites such as marrow and cortical bone, remains an obstacle to cure. 131I-labeled anti-CD45 antibody has been used to deliver radiation to marrow and lymphoid compartments when combined with myeloablative chemotherapy for the treatment of acute leukemia in adults. Dr. Park will examine the use of 131I-labeled BC8 (anti-CD45) antibody combined with the myeloablative chemotherapy regimen of topotecan, carboplatin and thiotepa in a Phase I trial treating patients with high risk neuroblastoma, with the goal of improving outcome by delivering additional therapy to MRD within the bone marrow. Dr. Park will receive didactic training in radiation biology, radiation physics, biostatistics and study design. Upon completion of the K23 award, she will have acquired a strong foundation in study design, therapeutic aspects of nuclear medicine and implementation of a clinical study, allowing her to emerge as an independent clinical investigator.